Five-Year Outcomes From the Randomized, Phase III Trials CheckMate 017 and 057: Nivolumab Versus Docetaxel in Previously Treated Non–Small-Cell Lung Cancer DOI Creative Commons
Hossein Borghaei, Scott Gettinger, Everett E. Vokes

et al.

Journal of Clinical Oncology, Journal Year: 2021, Volume and Issue: 39(7), P. 723 - 733

Published: Jan. 15, 2021

Immunotherapy has revolutionized the treatment of advanced non-small-cell lung cancer (NSCLC). In two phase III trials (CheckMate 017 and CheckMate 057), nivolumab showed an improvement in overall survival (OS) favorable safety versus docetaxel patients with previously treated, squamous nonsquamous NSCLC, respectively. We report 5-year pooled efficacy from these trials.Patients (N = 854; 017/057 pooled) ECOG PS ≤ 1, progression during or after first-line platinum-based chemotherapy were randomly assigned 1:1 to (3 mg/kg once every 2 weeks) (75 mg/m2 3 until unacceptable toxicity. The primary end point for both was OS; secondary points included progression-free (PFS) safety. Exploratory landmark analyses investigated.After minimum follow-up 64.2 64.5 months 057, respectively, 50 nivolumab-treated nine docetaxel-treated alive. Five-year OS rates 13.4% 2.6%, respectively; PFS 8.0% 0%, Nivolumab-treated without disease at years had 82.0% 93.0% chance survival, a 59.6% 78.3% remaining 5 years, Treatment-related adverse events (TRAEs) reported 8 31 (25.8%) between 3-5 follow-up, seven whom experienced new events; one (3.2%) TRAE grade 3, there no 4 TRAEs.At continued demonstrate benefit docetaxel, exhibiting five-fold increase rate, signals. These data represent first outcomes randomized programmed death-1 inhibitor NSCLC.

Language: Английский

Lung cancer DOI
Alesha Thai, Benjamin Solomon, Lecia V. Sequist

et al.

The Lancet, Journal Year: 2021, Volume and Issue: 398(10299), P. 535 - 554

Published: July 21, 2021

Language: Английский

Citations

1704
Atezolizumab for First-Line Treatment of PD-L1–Selected Patients with NSCLC DOI Open Access
Roy S. Herbst, Giuseppe Giaccone, Filippo de Marinis

et al.

New England Journal of Medicine, Journal Year: 2020, Volume and Issue: 383(14), P. 1328 - 1339

Published: Sept. 30, 2020

The efficacy and safety of the anti-programmed death ligand 1 (PD-L1) monoclonal antibody atezolizumab, as compared with those platinum-based chemotherapy, first-line treatment for patients metastatic non-small-cell lung cancer (NSCLC) PD-L1 expression are not known.We conducted a randomized, open-label, phase 3 trial involving nonsquamous or squamous NSCLC who had previously received chemotherapy on at least 1% tumor cells tumor-infiltrating immune assessed by SP142 immunohistochemical assay. Patients were assigned in 1:1 ratio to receive atezolizumab chemotherapy. Overall survival (primary end point) was tested hierarchically according status among intention-to-treat population whose tumors wild-type respect EGFR mutations ALK translocations. Within tumors, overall progression-free also prospectively subgroups defined findings two assays well blood-based mutational burden.Overall, 572 enrolled. In subgroup highest (205 patients), median longer 7.1 months group than (20.2 vs. 13.1 months; hazard death, 0.59; P = 0.01). Among all could be evaluated safety, adverse events occurred 90.2% 94.7% group; grade 4 30.1% 52.5% respective groups. favored high burden.Atezolizumab resulted significantly expression, regardless histologic type. (Funded F. Hoffmann-La Roche/Genentech; IMpower110 ClinicalTrials.gov number, NCT02409342.).

Language: Английский

Citations

1325
First-line nivolumab plus ipilimumab combined with two cycles of chemotherapy in patients with non-small-cell lung cancer (CheckMate 9LA): an international, randomised, open-label, phase 3 trial DOI
Luis Paz‐Ares, Tudor‐Eliade Ciuleanu, Manuel Cobo

et al.

The Lancet Oncology, Journal Year: 2021, Volume and Issue: 22(2), P. 198 - 211

Published: Jan. 19, 2021

Language: Английский

Citations

1088
PD-L1 as a biomarker of response to immune-checkpoint inhibitors DOI
Deborah B. Doroshow, Sheena Bhalla, Mary Beth Beasley

et al.

Nature Reviews Clinical Oncology, Journal Year: 2021, Volume and Issue: 18(6), P. 345 - 362

Published: Feb. 12, 2021

Language: Английский

Citations

1074
Recommendations for the use of next-generation sequencing (NGS) for patients with metastatic cancers: a report from the ESMO Precision Medicine Working Group DOI Creative Commons

F. Mosele,

Jordi Remón, Joaquı́n Mateo

et al.

Annals of Oncology, Journal Year: 2020, Volume and Issue: 31(11), P. 1491 - 1505

Published: Aug. 24, 2020

Language: Английский

Citations

948
First-line nivolumab plus ipilimumab in unresectable malignant pleural mesothelioma (CheckMate 743): a multicentre, randomised, open-label, phase 3 trial DOI
Paul Baas, Arnaud Scherpereel, Anna K. Nowak

et al.

The Lancet, Journal Year: 2021, Volume and Issue: 397(10272), P. 375 - 386

Published: Jan. 1, 2021

Language: Английский

Citations

943
The 2021 WHO Classification of Lung Tumors: Impact of Advances Since 2015 DOI Creative Commons
Andrew G. Nicholson, Ming‐Sound Tsao, Mary Beth Beasley

et al.

Journal of Thoracic Oncology, Journal Year: 2021, Volume and Issue: 17(3), P. 362 - 387

Published: Nov. 20, 2021

Language: Английский

Citations

919
Combination strategies with PD-1/PD-L1 blockade: current advances and future directions DOI Creative Commons
Ming Yi, Xiaoli Zheng,

Mengke Niu

et al.

Molecular Cancer, Journal Year: 2022, Volume and Issue: 21(1)

Published: Jan. 21, 2022

Antibodies targeting programmed cell death protein-1 (PD-1) or its ligand PD-L1 rescue T cells from exhausted status and revive immune response against cancer cells. Based on the immense success in clinical trials, ten α-PD-1 (nivolumab, pembrolizumab, cemiplimab, sintilimab, camrelizumab, toripalimab, tislelizumab, zimberelimab, prolgolimab, dostarlimab) three α-PD-L1 antibodies (atezolizumab, durvalumab, avelumab) have been approved for various types of cancers. Nevertheless, low rate α-PD-1/PD-L1 therapy remains to be resolved. For most patients, PD-1/PD-L1 pathway is not sole speed-limiting factor antitumor immunity, it insufficient motivate effective by blocking axis. It has validated that some combination therapies, including plus chemotherapy, radiotherapy, angiogenesis inhibitors, targeted therapy, other checkpoint agonists co-stimulatory molecule, stimulator interferon genes agonists, fecal microbiota transplantation, epigenetic modulators, metabolic superior efficacies higher rates. Moreover, bifunctional bispecific containing moiety also elicited more potent activity. These strategies simultaneously boost multiple processes cancer-immunity cycle, remove immunosuppressive brakes, orchestrate an immunosupportive tumor microenvironment. In this review, we summarized synergistic mechanisms with therapies. focused advances α-PD-1/PD-L1-based immunomodulatory studies. Given heterogeneity across patients types, individualized selection could improve effects relieve treatment resistance.

Language: Английский

Citations

879
RAS-targeted therapies: is the undruggable drugged? DOI Open Access
Amanda R. Moore, Scott Rosenberg, Frank McCormick

et al.

Nature Reviews Drug Discovery, Journal Year: 2020, Volume and Issue: 19(8), P. 533 - 552

Published: June 11, 2020

Language: Английский

Citations

822
NCCN Guidelines Insights: Non–Small Cell Lung Cancer, Version 2.2021 DOI Open Access
David S. Ettinger, Douglas E. Wood, Dara L. Aisner

et al.

Journal of the National Comprehensive Cancer Network, Journal Year: 2021, Volume and Issue: 19(3), P. 254 - 266

Published: March 1, 2021

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Non–Small Cell Lung Cancer (NSCLC) address all aspects of management NSCLC. These Insights focus on recent updates to the regarding targeted therapies, immunotherapies, and their respective biomarkers.

Language: Английский

Citations

818